Opipramol dihydro­chloride

Richard Betz; Thomas Gerber; Eric Hosten; Budanoor P Siddaraju; Hemmige S Yathirajan

doi:10.1107/S1600536811042280

. 2011 Oct 22;67(Pt 11):o2994–o2995. doi: 10.1107/S1600536811042280

Opipramol dihydrochloride

Richard Betz ^a,^*, Thomas Gerber ^a, Eric Hosten ^a, Budanoor P Siddaraju ^b, Hemmige S Yathirajan ^b

PMCID: PMC3247396 PMID: 22220014

Abstract

The title compound (systematic name: 4-{3-[2-azatricyclo[9.4.0.0^3,8]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl]propyl}-1-(2-hydroxyethyl)piperazine-1,4-diium dichloride), C₂₃H₃₁N₃O⁺·2Cl⁻, is the dihydrochloride of a piperazine derivative bearing a bulky 3-(5H-dibenz[b,f]azepin-5-yl)propyl substituent. Protonation took place on both N atoms of the piperazine unit. The diazacyclohexane ring adopts a chair conformation. N—H⋯Cl, O—H⋯Cl and C—H⋯Cl hydrogen bonding as well as C—H⋯O contacts connect the components into a three-dimensional network in the crystal. Two C—H⋯π contacts are also observed.

Related literature

For applications of opipramol, see: Moller et al. (2001 ▶). For related structures, see: Jasinski et al. (2010 ▶); Fun et al. (2011 ▶); Siddegowda, Butcher et al. (2011 ▶); Siddegowda, Jasinski et al. (2011 ▶); Swamy et al. (2007 ▶). For graph-set analysis of hydrogen bonds, see: Etter et al. (1990 ▶); Bernstein et al. (1995 ▶). For puckering analysis, see: Cremer & Pople (1975 ▶); Boessenkool & Boeyens (1980 ▶).

Experimental

Crystal data

C₂₃H₃₁N₃O²⁺·2Cl⁻
M _r = 436.41
Orthorhombic,
a = 33.6581 (6) Å
b = 9.4265 (2) Å
c = 6.8978 (1) Å
V = 2188.52 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.32 mm⁻¹
T = 200 K
0.51 × 0.27 × 0.14 mm

Data collection

Bruker APEXII CCD diffractometer
20068 measured reflections
5253 independent reflections
4854 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.027
wR(F ²) = 0.071
S = 1.03
5253 reflections
274 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.21 e Å⁻³
Absolute structure: Flack (1983 ▶), 2293 Friedel pairs
Flack parameter: −0.004 (33)

Data collection: APEX2 (Bruker, 2010 ▶); cell refinement: SAINT (Bruker, 2010 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811042280/mw2030sup1.cif

e-67-o2994-sup1.cif^{(30.4KB, cif)}

Supplementary material file. DOI: 10.1107/S1600536811042280/mw2030Isup2.cdx

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811042280/mw2030Isup3.hkl

e-67-o2994-Isup3.hkl^{(257.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811042280/mw2030Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg2 is the centroid of the C11–C16 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H81⋯Cl1ⁱ	0.79 (2)	2.39 (2)	3.1701 (14)	169 (2)
N2—H72⋯Cl1	0.82 (2)	2.212 (19)	3.0057 (13)	163.0 (15)
N3—H73⋯Cl2ⁱⁱ	0.98 (3)	2.03 (3)	2.9972 (12)	171 (2)
C5—H5A⋯Cl1ⁱⁱⁱ	0.99	2.82	3.7065 (15)	149
C5—H5A⋯O1ⁱⁱ	0.99	2.59	3.3373 (18)	133
C14—H14⋯Cl1^iv	0.95	2.83	3.7233 (14)	157
C31—H31A⋯O1ⁱⁱ	0.99	2.54	3.2446 (18)	128
C31—H31B⋯Cl2^v	0.99	2.75	3.5518 (14)	139
C32—H32B⋯Cl1ⁱⁱ	0.99	2.85	3.8246 (13)	169
C32—H32A⋯Cl2^vi	0.99	2.85	3.7213 (16)	148
C6—H6B⋯Cl2^vi	0.99	2.76	3.6634 (18)	152
C34—H34A⋯Cl2	0.99	2.82	3.5471 (13)	131
C16—H16⋯Cg2^iv	0.95	2.98	3.6402 (16)	128
C23—H23⋯Cg2^vii	0.95	2.67	3.4805 (18)	143

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) .

Acknowledgments

BPS thanks the University of Mysore for research facilities. HSY thanks R. L. Fine Chem., Bengaluru, for the gift sample of the title compound.

supplementary crystallographic information

Comment

Opipramol (systematic IUPAC name: 4-(3-{2-azatricyclo[9.4.0.0^3,8]pentadeca- 1(15),3,5,7,11,13-hexaen-2-yl}propyl)-1-(2-hydroxyethyl)piperazin-1,4-diium dichloride is an antidepressant and anxiolytic typically used in the treatment of generalized anxiety disorder (Moller et al., 2001). Opipramol is a tricyclic compound with no reuptake-inhibiting properties. However, it has pronounced D2-, 5-HT2-, and H1-blocking potential and high affinity to sigma receptors (sigma-1 and sigma-2). The crystal structures of opipramol dipicrate (Jasinski et al., 2010), opipramol (Fun et al., 2011), opipramolium fumarate (Siddegowda, Butcher et al., 2011) and flupentixol dihydrochloride (Siddegowda, Jasinski et al., 2011) have been reported recently. In view of the importance of the title compound we herein report its molecular and crystal structure.

Protonation took place exclusively on both nitrogen atoms of the piperazine unit. The diazacyclohexane ring adopts a ⁴C₁ (^N3C_N2) conformation (Cremer & Pople, 1975). The more rigid skeleton of the seven-membered ring adopts a conformation in between a TC2 and a C6 conformation (Q₂: 0.6128 (14) Å, Q₃: 0.2043 (14) Å, π₂: 177.14 (14)°, π₃: 178.9 (4)°) (Boessenkool & Boeyens, 1980). The nitrogen atom sticks out of the least-squares plane defined by its atoms by 0.451 (1) Å (Fig. 1).

Apart from classical hydrogen bonds of the N–H···Cl and the O–H···Cl type, the crystal structure features a multitude of C–H···Cl contacts and two C–H···O contacts whose ranges invariably fall at least 0.1 Å below the sum of van-der-Waals radii of the respective atoms participating. The C–H···Cl contacts involve hydrogen atoms of methylene groups – both intracyclic as well as those on the hydroxyethyl side-chain – as well as one hydrogen atom on a phenyl ring. The C–H···O contacts all involve hydrogen atoms of the methylene groups located in the piperazine moiety and in the hydrocarbon chain connecting this to the remainder of the molecule. Both chloride anions attain pentacoordination via their combined contacts with hydrogen atoms, however, one of the anions features four instead of three C–H-supported contacts. In terms of graph-set analysis (Etter et al., 1990; Bernstein et al., 1995), the descriptor for the classical hydrogen bonds is DDD on the unitary level while the C–H···O contacts require a C¹₁(7)C¹₁(9) descriptor on the same level. A DDDDDDD descriptor on the unitary level is necessary to capture the C–H···Cl contacts. Furthermore, two C–H···C_g contacts can be observed involving hydrogen atoms on the phenyl rings as donors and the phenyl moiety comprised of the carbon atoms C11–C16. All of these interactions serve to connect the cations and anions into a three-dimensional network in the crystal. The shortest intercentroid distance between two aromatic systems was measured at 4.7319 (9) Å and is apparent between two different phenyl moieties.

The packing of the title compound in the crystal is shown in Figure 2.

Experimental

The title compound was obtained as a gift sample from R. L. Fine Chem. Ltd., Bangalore, India. The compound was recrystallized from a 1:1 mixture of butan-1-one and benzene.